Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis

Abstract

Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients' survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76-2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58-2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75-2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05-3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41-2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46-2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42-4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30-4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46-3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40-5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95% CIREM: 1.06-2.27; PREM = 0.187) and in gastric cancer patients with positive lymph node metastasis (ORREM = 2.37, 95% CIREM: 1.19-4.73; PREM = 0.004) and intestinal-type classification (ORREM = 2.34, 95% CIREM: 1.59-3.45; PREM = 0.767). Our findings provide evidence that MUC1 detection has a prognostic value in patients with epithelial-originated cancers, especially in NSCLC and gastrointestinal cancers.

FIGURE 1

PRISMA flowchart of the literature search.

FIGURE 2

Forest plots of studies evaluating hazard ratios (HRs) of MUC1 for overall survival with a fixed effect model. HRs = hazard ratios, MUC1 = mucin 1.

FIGURE 3

Forest plots of studies evaluating hazard ratios (HRs) of MUC1 for overall survival with a random effect model. HRs = hazard ratios, MUC1 = mucin 1.

FIGURE 4

Forest plots of studies evaluating the association between MUC1 and clinical parameters in CRC and GC with a random effect model. (A) Tumor node metastasis (TNM) stage (advanced vs early) in CRC; (B) lymph node metastasis (present vs absent) in GC; (C) Lauren classification (intestinal-type vs diffuse-type) in GC; (D) TNM stage (advanced vs early) in GC. CRC = colorectal cancer, GC = gastric carcinoma, MUC1 = mucin 1.

FIGURE 5

Effect of individual studies on the pooled HR for MUC1 and OS of patients. HR = hazard ratio, MUC1 = mucin 1, OS = overall survival.

FIGURE 6

Begg's funnel plots for all of the included studies reported with OS. OS = overall survival.